Sialuria due to GNE pathogenic variant masquerading as cerebral palsy

Dear Editor,

Sialuria (OMIM#269921) is an inborn error of metabolism that leads to abnormally high free sialic acid and occurs due to mutations dominant mutations in the GNE gene.^[1] A total of ten case studies have been published to date. Here, we report the 11^th case from the world and the first Indian case of Sialuria, which masqueraded as cerebral palsy.

A 7-year-old male child, without any significant family and birth history presented with developmental delay and seizures from 6 months of age. The child had a global developmental delay with a predominant delay in the motor domain. He currently walks with difficulty, needs help for activities of daily living, and speaks in phrases with dysarthria. Seizures were noted at 6 months of age, with frequency of 1–2 episodes per year, requiring 2 antiseizure medications. The child also had stiffness of limbs starting from 2 years of age. On examination, weight -15.5 kg, height -101 cm, and head circumference -48 cm all are <3. Standard deviation, spasticity in all four limbs, exaggerated deep tendon reflexes, and extensor planters. Hepatosplenomegaly and coarse facies were absent. On investigations, complete hemograms, liver and kidney function tests, ammonia, lactate, blood gases, and tandem mass spectrometry were normal. Magnetic resonance imaging (MRI) brain showed mild cerebral atrophy with dilated ventricles. Exome sequencing identified a likely pathogenic missense variant c.2086G>A, p.(Val696Met) in the GNE gene. Parents did not consent to testing. Urinary total N-Acetylneuraminic acid: 1.4 (0.41 ± 0.23 mmol/g creatinine) and Free N-Actylneuraminic acid: 1.0 (0.24 + 0.14 mmol/g creatinine) was elevated.

In summary, the child has a global developmental delay, seizures, and spastic quadriparesis with no organomegaly, which prompted us to think of cerebral palsy, hereditary spastic paraparesis, and arginase deficiency. Exome sequencing gave us a clue like the case identified by Champaigne et al.^[2] On reverse phenotyping and biochemical investigation, the diagnosis of sialuria was confirmed. Mutations affecting the allosteric site Arg 263 and Arg 266 and other variants like p.Asp84 His have been described.^[3] The mutation in the current case does not lie in the allosteric domain and awaits explanation by further functional studies. In conclusion, any child with cerebral palsy and no significant birth history or changes on an MRI brain scan should be investigated for genetic aetiology.